Taglauer Elizabeth S, Wachman Elisha M, Juttukonda Lillian, Klouda Timothy, Kim Jiwon, Wang Qiong, Ishiyama Asuka, Hackam David J, Yuan Ke, Jia Hongpeng
bioRxiv. 2021 Nov 22:2021.11.19.469335. doi: 10.1101/2021.11.19.469335.
Human placental tissues have variable rates of SARS-CoV-2 invasion resulting in consistently low rates of fetal transmission suggesting a unique physiologic blockade against SARS-CoV-2. Angiotensin-converting enzyme (ACE)-2, the main receptor for SARS-CoV-2, is expressed as cell surface and soluble forms regulated by a metalloprotease cleavage enzyme, ADAM17. ACE-2 is expressed in the human placenta, but the regulation of placental ACE-2 expression in relation to timing of maternal SARS-CoV-2 infection in pregnancy is not well understood. In this study, we evaluated ACE-2 expression, ADAM17 activity and serum ACE-2 abundance in a cohort of matched villous placental and maternal serum samples from Control pregnancies (SARS-CoV-2 negative, n=8) and pregnancies affected by symptomatic maternal SARS-CoV-2 infections in the 2 trimester ("2 Tri COVID", n=8) and 3rd trimester ("3 Tri COVID", n=8). In 3 Tri COVID as compared to control and 2 Tri-COVID villous placental tissues ACE-2 mRNA expression was remarkably elevated, however, ACE-2 protein expression was significantly decreased with a parallel increase in ADAM17 activity. Soluble ACE-2 was also significantly increased in the maternal serum from 3 Tri COVID infections as compared to control and 2 Tri-COVID pregnancies. These data suggest that in acute maternal SARS-CoV-2 infections, decreased placental ACE-2 protein may be the result of ACE-2 shedding. Overall, this work highlights the importance of ACE-2 for ongoing studies on SARS-CoV-2 responses at the maternal-fetal interface.
人胎盘组织对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的侵袭率各不相同，导致胎儿传播率一直较低，这表明存在一种针对SARS-CoV-2的独特生理屏障。血管紧张素转换酶（ACE）-2是SARS-CoV-2的主要受体，以细胞表面形式和可溶性形式表达，受金属蛋白酶裂解酶ADAM17调控。ACE-2在人胎盘中表达，但胎盘ACE-2表达与孕期母体SARS-CoV-2感染时间的关系尚不清楚。在本研究中，我们评估了来自对照妊娠（SARS-CoV-2阴性，n=8）以及妊娠中期（“妊娠中期COVID”，n=8）和妊娠晚期（“妊娠晚期COVID”，n=8）出现症状性母体SARS-CoV-2感染的妊娠的一组匹配的绒毛胎盘和母体血清样本中的ACE-2表达、ADAM17活性和血清ACE-2丰度。与对照和妊娠中期COVID绒毛胎盘组织相比，妊娠晚期COVID绒毛胎盘组织中ACE-2 mRNA表达显著升高，然而，ACE-2蛋白表达显著降低，同时ADAM17活性平行增加。与对照和妊娠中期COVID妊娠相比，妊娠晚期COVID感染的母体血清中可溶性ACE-2也显著增加。这些数据表明，在急性母体SARS-CoV-2感染中，胎盘ACE-2蛋白减少可能是ACE-2脱落的结果。总体而言，这项工作突出了ACE-2在母婴界面SARS-CoV-2反应的 ongoing 研究中的重要性。 （注：“ongoing”此处翻译为“正在进行的”，但感觉原文此处表述不太准确，可能是想表达“持续的”之类意思，不过按照要求准确翻译了）
